Role of transforming growth factor beta 1 in induction of colon carcinoma differentiation by hexamethylene bisacetamide.
The differentiation agent hexamethylene bisacetamide (HMBA) increased expression of transforming growth factor beta 1 (TGF beta 1) mRNA in HT29 colon carcinoma cells. The increase was evident after 24 h and was maintained at levels 4-5-fold the control levels for at least 5-13 days. No increase in expression of TGF beta 2 or TGF alpha mRNA was observed. Both TGF beta 1 and HMBA induced loss of expression of a cell surface malignancy marker on HT29 cells, and both decreased cell growth in serum-free medium. Exogenously applied TGF beta 1 mimicked the growth-arresting effect of HMBA on three surgically resected moderately differentiated colon carcinomas in serum-free primary culture. Both TGF beta 1 and HMBA increased the tumor growth fraction in a second group of three more aggressive colon carcinomas, while neither agent had any measurable growth-modulating activity on two other colon carcinomas. The induction of TGF beta 1 mRNA by HMBA along with the parallel biological effects of HMBA and exogenously applied TGF beta 1 on resected carcinomas and on HT29 cells suggest that the effects of HMBA on colon carcinoma cells may be mediated in part by induction of TGF beta 1.
Schroy
P
P
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
Rifkin
J
J
Coffey
R J
RJ
Winawer
S
S
Friedman
E
E
D000081:Acetamides / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000473:pathology*; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis; D015291:Transforming Growth Factors / Q000235:genetics / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000081:Acetamides; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D015291:Transforming Growth Factors; C014026:hexamethylene bisacetamide